title: Effects of luminal thymol on epithelial transport in human and rat colon.
abstract: Gut lumen is continually exposed to a great variety of agents, including noxious compounds. Chemical receptors that detect the luminal environment are thought to play an important role as sensors and to modulate gastrointestinal functions. Recently, it has been reported that odorant receptors (ORs) are expressed in the small intestinal mucosa and that odorants stimulate serotonin secretion. However, ion transport in the responses to odorants has rarely been discussed, particularly in relation to the large intestine. In the present study, we examined the effects of the OR ligand thymol on ion transport in human and rat colonic epithelia using an Ussing chamber. In the mucosal-submucosal preparations, the mucosal addition of thymol evoked anion secretion concentration dependently. In addition, dextran (4 kDa) permeability was enhanced by the mucosal treatment with thymol. The response to thymol was not affected by tetrodotoxin (TTX) or piroxicam treatments in human or rat colon. Thymol-evoked electrogenic anion secretion was abolished under Ca(2+)-free conditions or mucosal treatment with transient receptor potential (TRP) A1 blocker (HC-030031). Pretreatment of thymol did not affect electrical field stimulation-evoked anion secretion but significantly attenuated short-chain fatty acid-evoked secretion in a concentration-dependent manner. OR1G1 and TRPA1 expression was investigated in isolated colonic mucosa by RT-PCR. The present results provide evidence that the OR ligand thymol modulates epithelial permeability and electrogenic anion secretion in human and rat colon. The anion secretion by luminal thymol is most likely mediated by direct activation of TRPA1 channel. We suggest that the sensing and responding to odorants in the colon also plays a role in maintaining intestinal homeostasis.
authors.affiliation: Laboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, Institute of Environmental Sciences, University of Shizuoka, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Kaji
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Karaki
authors.forename: Atsukazu
authors.initials: A
authors.lastname: Kuwahara
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018035:Receptors, Odorant / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D013943:Thymol / Q000494:pharmacology*; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D017487:Ankyrins; D001639:Bicarbonates; D015220:Calcium Channels; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D003911:Dextrans; D005227:Fatty Acids; D009419:Nerve Tissue Proteins; C533784:OR1G1 protein, human; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D018035:Receptors, Odorant; D012702:Serotonin Antagonists; D026941:Sodium Channel Blockers; D049994:Sodium Potassium Chloride Symporter Inhibitors; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C480976:Trpa1 protein, rat; D013943:Thymol; D012964:Sodium; D010738:Type C Phospholipases; D002118:Calcium